Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer

NCT03162224 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 1 other identifier: D8860C00005
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

Brief Summary

This is a Phase 1b/2a, open-label, multi-center study to evaluate the safety and tolerability, anti-tumor activity, and immunogenicity of MEDI0457 (also known as INO 3112) a HPV Deoxyribonucleic Acid (DNA) vaccine in combination with durvalumab (also known as MEDI4736) which is a human monoclonal antibody directed against Programmed Death Ligand 1 (PD-L1), which blocks the interaction of PD-L1 with PD-1 and Cluster of differentiation 80 (CD80). An initial three to 12 participants (Safety Analysis Run-in participants) will be enrolled and assessed for safety before additional participants are enrolled. The initial safety analysis run-in participants along with an approximate total of 50 participants with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer (HNSCC) will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.

Conditions

Head and Neck Cancer; Human Papilloma Virus

Keywords

Head and Neck Squamous Cell Carcinoma; Oropharyngeal Cancer; HPV; Human Papilloma Virus; Cancer Immunotherapy; Check point inhibitors; PD-L1 inhibitor; Recurrent or Metastatic Cancer; Durvalumab; MEDI0457; Antineoplastic agents; Neoplasms

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measures at the time of end of study.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs

  Any laboratory abnormality during analysis of hematology, clinical chemistry, thyroid function tests, and urinalysis that was new in onset or worsened in severity or frequency from the baseline condition and required therapeutic intervention or diagnostic tests, led to discontinuation of study treatment, had accompanying or inducing symptoms or signs, or judged by the Investigator as clinically significant was recorded as AE. Participants with abnormal laboratory parameters reported as TEAEs are reported.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs

  Participants with ECG abnormalities reported as TEAEs are reported.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs

  Vital sign assessment included body temperature, respiration rate, pulse oximetry, blood pressure, heart rate, and weight. Participants with abnormal vital sign and/or abnormal physical examination reported as TEAEs are reported.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Number of Participants Who Received Any Concomitant Medications During the Study

  Participants who received concomitant medications which were ongoing at the start of treatment or started after the study treatment are included.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status

  Participants with shift \>=3 changed from baseline in ECOG status are reported. ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. The scores are: 0 = Fully Active, able to carry out all pre-disease performance without restrictions; 1 = Restricted activity but ambulatory and able to carry out light work or work of a sedentary nature; 2 = Ambulatory and capable of self-care but unable to carry out work activities; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely Disabled, unable to carry out any self-care and totally confined to bed or chair; 5 = Dead.

  Day 1 through 90 days after the last dose of study drug (approximately 45 months)

• Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population

  The objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.

  Day 1 through end of study (approximately 45 months)

Secondary Outcomes (9)

• Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population

  Day 1 through end of study (approximately 45 months)

• Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population

  Day 1 through end of study (approximately 45 months)

• Percentage of Participants With Objective Response by irRECIST in As-treated Population

  Day 1 through end of study (approximately 45 months)

• Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population

  Week 16

• DCR at Week 16 by RECIST Version 1.1 in As-treated Population

  Week 16

Study Arms (3)

First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory

EXPERIMENTAL

Participants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.

Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab

1L R/M Platinum Refractory

EXPERIMENTAL

Participants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.

Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab

Second-line (2L) + R/M

EXPERIMENTAL

Participants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.

Drug: MEDI0457; Device: CELLECTRA®5P device; Drug: Durvalumab

Interventions

MEDI0457 DRUG

MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device.

Also known as: INO-3112

1L R/M Platinum Refractory; First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory; Second-line (2L) + R/M

CELLECTRA®5P device DEVICE

MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device.

Also known as: CELLECTRA 2000

1L R/M Platinum Refractory; First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory; Second-line (2L) + R/M

Durvalumab DRUG

Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks.

Also known as: MEDI4736

1L R/M Platinum Refractory; First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory; Second-line (2L) + R/M

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants 18 years and older
• Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
• Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
• Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.

You may not qualify if:

• Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
• Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
• No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (14)

Research Site

San Francisco, California, 94115, United States

Location

Research Site

Orlando, Florida, 32806, United States

Location

Research Site

Atlanta, Georgia, 30308, United States

Location

Research Site

Indianapolis, Indiana, 46202, United States

Location

Research Site

Baltimore, Maryland, 21201, United States

Location

Research Site

Baltimore, Maryland, 21287, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

Minneapolis, Minnesota, 55414, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Morristown, New Jersey, 07960, United States

Location

Research Site

The Bronx, New York, 10461, United States

Location

Research Site

Winston-Salem, North Carolina, 27157, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• D8860C00005 SAP redacted
• CSP Redacted
• CSR Synopsis Redacted

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Recurrence; Neoplasm Metastasis; Neoplasms

Interventions

MEDI0457; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Limitations and Caveats

The expected response in terms of efficacy was not achieved at the time of DCO. It was therefore decided to stop further enrollment of participants and the study was terminated. There were no safety concerns were noted with the combination of MEDI0457 and durvalumab.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: Global Clinical Lead

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• MedImmune LLC

  Study Director

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 22, 2017
• Study Start: June 26, 2017
• Primary Completion: March 19, 2021
• Study Completion: March 19, 2021
• Last Updated: August 25, 2022
• Results First Posted: August 25, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (14)